The present invention relates to a cyanomethylene compound, a process for preparing the same and an agricultural and horticultural fungicide which contains the compound.
Recent years have seen the emergence of drug resistant fungi due to long term use of fungicides. For this reason, it has become difficult to accomplish control by use of known fungicides such as benzimidazole. Consequently, there is a demand for development of new type of compounds having a fungicidal activity against drug resistant fungi.
As a compound having a cyanomethylene group bonded to the 2-position on the thiazolidine ring, a compound represented by the formula (A) 
is disclosed, for example, in Phamazie, 53(6), 373-376 (1998) which reports that the compound has an antituberculous activity. However, the publication discloses nothing about the fungicidal activity of the compound of the formula (A).
WO96/33995 discloses oxopropionitrlle derivatives represented by the formula (B) 
wherein Ra is an alkyl group having 2 to 8 carbon atoms, Rb is a hydrogen atom, etc., Rc is a heterocyclic group and Rd is a hydrogen atom, etc., and mentions that the derivatives have an insecticidal activity, but refers nowhere to a fungicidal activity of the derivatives.
An object of the invention is to provide a novel cyanomethylene compound which exhibits an excellent fungicidal activity against drug resistant fungi as well as drug sensitive fungi.
Another object of the invention is to provide a process for preparing the cyanomethylene compound.
A further object of the invention is to provide a new type of fungicide for agriculture and horticulture which exhibits a remarkable fungicidal effect against chemical-resistant fungi as well as chemical-sensitive fungi.
The invention provides cyanomethylene compounds represented by the formula (1) (hereinafter referred to as xe2x80x9ccyanomethylene compound (1)xe2x80x9d) 
wherein R is C1-20 straight-chain or branched-chain alkyl, C3-8 cycloalkyl, aryl, aryl-C1-4 alkyl or heterocyclic group; and the aryl, the aryl-C1-4 alkyl and the heterocyclic group may be substituted with at least one substituent selected from the group consisting of halogen atom, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkoxycarbonyl, C1-4 alkylaminocarbonyl, C1-4 alkoxyimino-C1-4 alkyl, C1-4 alkylamino, C1-4 alkylcarbonyl, C1-4 alkylthio, aryl-C1-4 alkyl, carbamoyl, phenoxy, benzyloxy, nitro and cyano;
R1 is C1-8 straight-chain or branched-chaln alkyl, C3-8 cycloalkyl, aryl, aryl-C1-4 alkyl or heterocyclic group; and the aryl, the aryl-C1-4 alkyl and the heterocyclic group may be substituted with at least one substituent selected from the group consisting of halogen atom, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkoxycarbonyl, C1-4 alkylamino, di-C1-4 alkylamino, C2-4 alkenyl, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, phenyl, phenoxy, nitro and cyano;
A is C1-6 straight-chain or branched-chain alkylene, C2-6 straight-chain or branched-chain alkenylene, xe2x80x94CH2xe2x80x94Bxe2x80x94CH2xe2x80x94 (wherein B is phenylene), xe2x80x94CH2xe2x80x94Oxe2x80x94Bxe2x80x94CH2xe2x80x94 (wherein B is as defined above) or xe2x80x94Zxe2x80x94COxe2x80x94 (wherein Z is C1-4 alkylene); and
Y is a sulfur atom, sulfinyl or sulfonyl.
The cyanomethylene compound (1) of the invention has a broad fungicidal spectrum, and an excellent fungicidal activity of controlling chemical-resistant fungi as well as chemical-sensitive fungi.
E/Z isomers are present in the cyanomethylene compound (1) of the invention. The cyanomethylene compound (1) of the invention includes an E/Z isomer and a mixture of E/Z isomers.
The invention provides a process for preparing the cyanomethylene compound (1), the process comprising reacting:
an isothiocyanate represented by the formula (2)
R1-NCSxe2x80x83xe2x80x83(2)
wherein R1 is as defined above;
an acetonitrile represented by the formula (3)
Rxe2x80x94Yxe2x80x94CH2xe2x80x94CNxe2x80x83xe2x80x83(3)
wherein R and Y are as defined above, and
a halogen compound represented by the formula (4)
X1xe2x80x94Axe2x80x94X2xe2x80x83xe2x80x83(4)
wherein A is as defined above, and X1 and X2 are the same or different and each represents halogen atom.
The invention provides a fungicide containing the cyanomethylene compound (1) for use in agriculture and horticulture.
In the formula (1), the groups represented by each of R, R1, A and Z can be exemplified as follows.
Examples of C1-20 straight-chain or branched-chain alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-trldecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl and the like.
Examples of C3-8 cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.
Examples of aryl are phenyl, naphthyl and the like.
Examples of aryl-C1-4 alkyl are benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl and the like.
Examples of heterocyclic group are pyridyl, pyrimidyl, benzotriazolyl, 1,2,4-triazole-1-yl, 2-thienyl, pyrazinyl, pyridazinyl, 2-benzothiazolyl, oxazolyl, isoxazolyl, thiazolyl, 8-quinolyl, oxadiazolyl and the like.
Examples of halogen atom are fluorine, chlorine, bromine, iodine and the like.
Examples of C1-4 alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and like C1-4 straight-chain or branched-chain alkyl groups.
Examples of C1-4 haloalkyl are fluoromethyl, bromomethyl, iodomethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 1-fluoroethyl, pentafluoroethyl, 1-fluoropropyl, 2-chloropropyl, 3-fluoropropyl, 3-chloropropyl, 1-fluorobutyl, 1-chlorobutyl, 4-fluorobutyl and like straight-chain or branched-chain alkyl substituted with 1 to 9 halogen atoms.
Examples of C1-4 alkoxy are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy and like C1-4 straight-chain or branched-chain alkoxy groups.
Examples of C1-4 haloalkoxy are fluoromethoxy, chloromethoxy, bromomethoxy, iodomethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 1-fluoroethoxy, 2,2,2-trifluoroethoxy, pentafluoroethoxy, 1-fluoropropoxy, 2-chloropropoxy, 3-fluoropropoxy, 3-chloropropoxy, 1-fluorobutoxy, 1-chlorobutoxy, 4-fluorobutoxy and like straight-chain or branched-chain alkoxy groups substituted with 1 to 9 halogen atoms.
Examples of C1-4 alkoxycarbonyl are methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl and like alkoxycarbonyl groups wherein the alkoxy moiety is C1-4 straight-chain or branched-chain alkoxy.
Examples of C1-4 alkylaminocarbonyl are methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, n-butylaminocarbonyl, isobutylaminocarbonyl, sec-butylaminocarbonyl, tert-butylaminocarbonyl and like alkylaminocarbonyl groups wherein the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C1-4 alkoxyimino-C1-4 alkyl are methoxyiminomethyl, ethoxyiminomethyl, 1-(n-propoxyimino)ethyl, isopropoxyiminomethyl, 2-(n,-butoxyimino)ethyl, sec-butoxyiminomethyl, tert-butoxyiminomethyl and like alkoxyiminoalkyl groups wherein the alkoxy moiety is C1-4 straight-chain or branched-chain, and the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C1-4 alkylamino are methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino and like alkylamino groups wherein the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C1-4 alkylcarobonyl are methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl and like alkylcarbonyl groups wherein the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C1-8 straight-chain or branched-chain alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl and the like.
Examples of di-C1-4 alkylamino group are dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, di-n-butylamino, diisobutylamino, sec-butylamino, di-tert-butylamino and like dialkylamino groups wherein the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C2-4 alkenyl are vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl and the like.
Examples of C1-4 alkylthio are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio and like alkylthio groups wherein the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C1-4 alkylsulfinyl are methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulflnyl and like alkylsulfinyl groups wherein the alkyl moiety is C1-4 straight-chain or branched-chain alkyl.
Examples of C1-4 alkylsulfonyl are methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl and like alkylsulfonyl groups wherein the alkyl moiety is C1-4 straight-chaln or branched-chaln alkyl.
Examples of C1-6 straight-chain or branched-chain alkylene are methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, etc.
Examples of C2-6 straight-chain or branched-chain alkenylene are vinylidene, propylene, butenylene and the like.
Examples of C1-4 alkylene are methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene and the like.
Among the cyanomethylene compounds (1) of the invention, preferred are those of the formula (1) wherein R is C1-20 straight-chain or branched-chain alkyl, C3-8 cycloalkyl, phenyl, benzyl or heterocyclic group (the phenyl, the benzyl and the heterocyclic group may be substituted with at least one substituent selected from the group consisting of halogen atom, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 aLkoxycarbonyl, C1-4 alkylaminocarbonyl, C1-4 alkoxyimino-C1-4 alkyl, C1-4 alkylamino, C1-4 alkylcarbonyl, C1-4 alkylthio, carbamoyl, phenoxy, benzyloxy, nitro, and cyano); R1 is C1-8 straight-chain or branched-chain alkyl, C3-8 cycloalkyl, phenyl, benzyl or pyridyl (the phenyl, the benzyl and the pyridyl may be substituted with at least one substituent selected from the group consisting of halogen atom, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkoxycarbonyl, C1-4 alkylamino, di-C1-4 alkylamino, C2-4 alkenyl, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, phenyl, phenoxy, nitro and cyano); A is C1-6 straight-chain or branched-chain alkylene, C2-4 straight-chain or branched-chain alkenylene, or xe2x80x94CH2xe2x80x94Bxe2x80x94CH2xe2x80x94 (wherein B is phenylene); and Y is a sulfur atom, sulfinyl or sulfonyl.
Among the cyanomethylene compounds (1) of the invention, more preferred are those of the formula (1) wherein R is phenyl (the phenyl may be substituted with at least one sustituent selected from the group consisting of halogen atom, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylcarbonyl, C1-4 alkylthio and cyano); R1 is phenyl or pyridyl (the phenyl and the pyridyl may be substituted with at least one substituent selected from the group consisting of halogen atom, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkoxycarbonyl, C1-4 alkylamino, di-C1-4 alkylamino, C2-4 alkenyl, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, phenyl, phenoxy, nitro and cyano); A is C1-6 straight-chaln or branched-chain alkylene; and Y is a sulfur atom.
Among the cyanomethylene compounds (1) of the invention, especially preferred are those of the formula (1) wherein R is phenyl (the phenyl may be substituted with at least one substituent selected from the group consisting of halogen atom and C1-4 haloalkyl); R1 is phenyl or pyridyl (the phenyl and the pyridyl may be substituted with at least one substituent selected from the group consisting of halogen atom, C1-4 alkyl and C1-4 alkoxy); A is ethylene; and Y is a sulfur atom.
Among the cyanomethylene compounds (1), most preferred are those of the formula (1) wherein R is phenyl substituted with halogen atom (such as fluorine, chlorine or the like) in the 2-position of the phenyl, and with C1-4 haloalkyl (such as trlfluoromethyl) in the 5-position thereof.
Among the cyanomethylene compounds (1) of the invention, most preferred are those of the formula (1) wherein R1 is phenyl unsubstituted or substituted with halogen atom (such as fluorine, chlorine or the like), C1-4 alkyl (such as methyl) or C1-4 alkoxy (such as methoxy) in the 2-position of the phenyl, or pyridyl unsubstituted or substituted with C1-4 alkoxy (such as methoxy). Among the cyanomethylene compounds (1), preferred are those of the formula (1) wherein the pyridyl is 2-pyridyl or 3-pyridyl, and those of the formula (1) wherein the pyridyl is substituted with C1-4 aikoxy (such as methoxy) in the 2-position of the pyridyl.
The cyanomethylene compound (1) of the invention can be prepared, for example, by reacting:
an isbthiocyanate represented by the formula (2)
R1-NCSxe2x80x83xe2x80x83(2)
wherein R1 is as defined above;
an acetonitrile represented by the formula (3)
xe2x80x83Rxe2x80x94Yxe2x80x94CH2xe2x80x94CNxe2x80x83xe2x80x83(3)
wherein R and Y are as defined above, and
a halogen compound represented by the formula (4)
X1xe2x80x94Axe2x80x94X2xe2x80x83xe2x80x83(4)
wherein A is as defined above, and X1 and X2 are the same or different and each represents halogen atom.
The proportions of the isothiocyanate (2) and the acetonitrile (3) to be used in the reaction are not limited and can be suitably selected from a wide range. The acetonitrile (3) is usually used in an amount of 1 to 5 moles, preferably about 1 mole or in the vicinity thereof, per mole of the isothiocyanate (2).
The proportions of the isothiocyanate (2) and the halogen compound (4) to be used in the reaction are not limited and can be suitably selected from a wide range. The halogen compound (4) is usually used in an amount of 1 to 5 moles, preferably about 1 mole or in the vicinity thereof, per mole of the isothiocyanate (2).
Preferably the reaction of the invention is carried out in the presence of a base. Useful bases are a variety of known ones, and include, for example, sodium hydrogencarbonate, sodium carbonate, potassium hydrogencarbonate, potassium carbonate, sodium hydride, potassium hydride and like inorganic bases, triethylamine, pyridine and like organic bases. These bases can be used either alone or in combination. The amount of the base to be used is not limited and can be suitably selected from a wide range. Usually the base is used in a stoichiometric amount sufficient to entrap the hydrogen haiide produced by the reaction or in more than the stoichiometric amount, preferably the stoichiometric amount or about 1 to about 5 times the amount. When triethylamine, pyridine or like organic base is used, it can be used in large excess to serve also as a solvent.
The reaction of the invention is usually performed in a solvent. Useful solvents are not limited insofar as they are inert to the reaction of the invention, and include known solvents such as hexane, cyclohexane, heptane and like aliphatic or alicyclic hydrocarbons, benzene, chlorobenzene, toluene, xylene and like aromatic hydrocarbons, methylene chloride, dichloroethane, chloroform, carbon tetrachloride and like halogenated hydrocarbons, diethyl ether, tetrahydrofuran, dioxane and like ethers, dimethylformamide, dlmethylsulfoxide, combinations of 2 or more thereof, etc.
The reaction of the invention is carried out usually at a temperature in the range of from xe2x88x9220xc2x0 C. to the boiling point of the solvent used and is usually complete in about 0.5 to about 24 hours.
The raw materials used in preparing the cyanomethylene compound (1), i.e. the thiolsocyanate (2), the acetonitrile (3) and the halogen compound (4), are commercially readily available compounds or can be easily prepared by known processes.
The eyanomethylene compound (1) of the invention prepared by said process can be easily isolated from the reaction system and purified, for example, by known isolating and purifying means such as filtration, solvent extraction, distillation, recrystallization, column chromatography or the like.
The cyanomethylene compound (1) of the invention is used, for example, as an active ingredient for a fungicide.
The cyanomethylene compound (1) of the invention can be used as a fungicide by itself and can be used by being made into the desirable form such as an oil, emulsion, wettable powder, flowable preparation, granules, powder, aerosol, fumigant or the like. In this case, the content of the thiazolidine compound (1) of the invention is not limited and can be suitably selected from a wide range according to various conditions such as the form of preparation, kind of disease to be treated, kind of plant, severity of disease, place of application, time for application, method of application, chemicals to be used in combination (insecticide, nematicide, acariclde, fungicide, herbicide, plant growth control agent, synerglst, soil conditioner, etc.), amount and kind of fertilizer and so on. The content is usually about 0.01 to about 95% by weight, preferably about 0.1 to about 50% by weight, based on the total amount of the fungicidal preparation.
A fungicidal preparation containing the cyanomethylene compound (1) of the invention as the active ingredient can be produced according to known processes. For example, the cyanomethylene compound (1) of the invention may be mixed with a carrier such as a solid carrier, a liquid carrier, a gaseous carrier or the like. Optionally a surfactant and other adjuvant for preparation may be added.
Useful carriers can be any of known ones which are usually used in this field.
Examples of useful solid carriers are fine particles or granules of clays (kaolin clay, diatomaceous earth, synthetic hydrated silicon dioxide, bentonite, fubasami clay, acid clay and the like), talcs, ceramics, other inorganic minerals (cerite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica, etc.), chemical fertilizers (ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.), and so on.
Useful liquid carriers are, for example, water, alcohols (methanol, ethanol, etc.), ketones (acetone, methyl ethyl ketone, etc.), aromatic hydrocarbons (benzene, toluene, xylene, ethylbenzene, methylnaphthalene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, kerosene, light oil, etc.), esters (ethyl acetate, butyl acetate, etc.), nitrites (acetonitrile, isobutyronitrile, etc.), ethers (diisopropyl ether, dioxane, etc.), acid amides (N,N-dimethylformamide, N,N-dimethylacetamide, etc.), halogenated hydrocarbons (dichloromethane, trichloroethane, carbon tetrachloride, etc.), dimethylsulfoxide, soybean oil, cotton seed oil and like vegetable oils and so on.
Examples of useful gaseous carriers (propellants) are butane gas, LPG (liquefied petroleum gas), dimethyl ether, carbon dioxide, etc.
Examples of useful surfactants are alkyl ester sulfates, alkyl sulfonates, alkylarylsulfonates, alkyl aryl ethers, polyoxyethylenated products thereof, polyethylene glycol ethers, polyhydrlc alcohol esters, sugar alcohol compounds, etc.
Examples of useful adjuvants for preparation are casein, gelatin, polysaccharides (starch powder, gum arabic, cellulose compound, alginic acid, etc.), ligunin compounds, bentonite, saccharides, synthetic water-soluble polymers (polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid, etc.) and like fixing agents, PAP (acidic isopropyl phosphate), BBH (2,6-di-tert-butyl-4-methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, fatty acids, esters thereof and like stabilizers.
The fungicidal preparation of the invention thus obtained can be used as it is or as diluted with water. The preparation may be prepared by being mixed with any of insecticides, nematicides, acaricides, fungicides, herbicides, plant growth control agents, synergists, soil conditioners, etc. The preparation of the invention may be applied simultaneously with other preparations.
When the preparation of the invention is used as a fungicide for use in agriculture and horticulture, the amount of the preparation of the invention is not limited and can be suitably selected from a wide range according to various conditions such as the concentration of active ingredient, the form of preparation, kind of disease to be treated, kind of plant, severity of disease, time for application, method of application, chemicals to be used in combination (insecticide, nematicide, miticide, fungicide, herbicide, plant growth control agent, synergist, soil conditioner, etc.), amount and kind of a fertilizer and so on. The amount is usually about 0.001 to about 100 g per 100 m2 of the area. When an emulsion, wettable powder, flowable preparation or the like is used as diluted with water, the concentration of the fungicidal preparation is about 0.1 to about 1000 ppm, preferably about 1 to 500 ppm. The granules, particles or the like are applied as such without dilution.
The compound of the invention is characterized by having an excellent fungicidal activity and a broad spectrum of activity. The compound can be used for control of plant diseases ascribed to pathogenic fungi and resistant pathogenic fungi. Examples of such pathogenic fungi include those that cause or are resistant to fungicides to treat rice plant blast, rice plant sheath blight, apple powdery mildew, apple Atternaria blotch, persimmon powdery mildew, grape powdery mildew, barley powdery mildew, wheat powdery mildew, cucumber powdery mildew, tomato late blight, strawberry powdery mildew, tobacco powdery mildew and the like.